1. Field of the Invention
This invention embodies new and novel compounds useful as analgesics and/or narcotic antagonists and a new and novel total synthesis for their preparation.
2. Description of the Prior Art
A. Everette May and Hiroshi Kugita, J. Org. Chem. 26, 188 (1961) describe compounds having the formula ##STR1## in which R.sup.2 is H or methyl and R is methyl or phenethyl as being moderate to weak analgetics.
B. Everette May, Hiroshi Kugita and J. Harrison Ager, J. Org. Chem. 26, 1621 (1961) report compounds having the formula ##STR2## in which R is methyl or phenethyl, R.sup.1 is methyl or H, R.sub.3 is H, OH or methoxy as producing varying degrees of analgesia.
C. Everette May, Colin Chignell and J. Harrison Agar, J. Med. Chem. 8, 235 (1965) report compounds having the formula ##STR3## in which R.sup.1 is H or methyl and R.sup.2 is methyl as possessing analgetic activity.
D. Everette May and Hiroshi Kugita, J. Org. Chem. 26, 1954 (1961) report the compound having the formula ##STR4## in which R is methyl or phenethyl, R.sup.1 is H or methyl and R.sup.2 is H or acetyl as having analgetic activity.
E. Everette May and Seiichi Sato, J. Org. Chem. 26, 4536 (1961) report compounds having the formula ##STR5## in which R.sup.2 is H or methyl, R.sup.1 is methyl or ethyl, R.sup.3 is methyl or ethyl and R.sup.4 is H or acetyl as possessing analgetic activity.
F. N. B. Eddy and E. L. May published a review of 6,7-benzomorphans in Synthetic Analgetics, Pergamon Press (1966).
G. U.S. Pat. No. 3,853,889 describes the compound having the formula ##STR6## wherein R.sup.1 is selected from the group comprising H, (lower)alkyl, ##STR7## and (lower)alkenyl in which R.sup.6 is H or CH.sub.3, R.sup.2 is selected from the group comprising H, (lower)alkyl, ##STR8## and cinnamoyl, and R.sup.3 is H or (lower)alkyl; or a pharmaceutically acceptable acid acceptable acid addition salt thereof as possessing agonist/antagonist activity.
H. U.S. Pat. No. 3,891,657 describes the compounds having the formula ##STR9## wherein R.sup.1 is selected from the group comprising -CH.sub.2 -C.tbd.CH, -CH.sub.2 -CH=CH.sub.2, ##STR10## alkenyl in which R.sup.6 is H or CH.sub.3, R.sup.2 is selected from the group comprising H, (lower)alkyl, ##STR11## R.sup.5 is H, (lower)acyl, trichloroacetyl or cinnamoyl; R.sup.3 is H, CH.sub.3, C.sub.2 H.sub.5, n-C.sub.3 H.sub.7, -CH.sub.2 -CH=CH.sub.2 or -CH.sub.2 -C.tbd.CH, or a pharmaceutically acceptable acid addition salt thereof are analgetic agents, narcotic antagonists or intermediates in the preparation of such agents.
I. U.S. Pat. No. 3,285,922 reports morphinans and isomorphinans having the formula ##STR12## in which Y is cyclobutyl or cyclopropyl as possessing analgetic and/or narcotic antagonist activity.
J. M. Gates and T. Montzka [J. Med. Chem., 7, 127 (1964)] report the synthesis of morphinans and isomorphinans of the formula ##STR13## in which Y is cyclopropylmethyl, cyclobutylmethyl, -phenylcyclopropylmethyl, methyl, cyano, H, etc. and R.sup.1 is methyl or H.